Slow-wave activity homeostasis in the somatosensory cortex after spinal cord injury.

The cortical reorganization after spinal cord injury (SCI) involves a series of physiological changes that drive the expansion of the intact cortical area to the deafferented cortical area. These changes have always been studied under a stimulus-response paradigm, which demonstrates that the deafferented cortex becomes more responsive to stimulation of body regions above the level of the lesion. However, less is known about how permanent large-scale deafferentation affects spontaneous activity in the somatosensory cortex, an important physiological feature related to the processing of peripheral inputs and perception. Here we studied the spontaneous activity at two sites of the somatosensory cortex, corresponding to forepaw and hindpaw, and at three different time points after SCI: acute SCI, one week post-SCI and chronic SCI (1-3 months after injury). Electrophysiological recordings from anesthetized rats were obtained in conditions of slow-wave activity in order to compare features of the neural populations in periods of cortical up-states. Our data demonstrate that acute SCI reduces the excitability of cortical neurons during up-states in both the forepaw and the hindpaw cortex. One week after SCI, the properties of cortical neurons were similar to those under control conditions, indicating a homeostatic plasticity. Finally, chronic SCI increased neural activity during up-states, while reduced up-state frequency in the cortex. We conclude that SCI induces different homeostatic changes in cortical slow-wave depending on the time after lesion. This temporal evolution of spontaneous activity could help better understand the cortical plasticity associated with acute or chronic SCI.

Increased responses in the somatosensory thalamus immediately after spinal cord injury.

Spinal cord injury (SCI) involves large-scale deafferentation of supraspinal structures in the somatosensory system, producing well-known long-term effects at the thalamo-cortical level. We recently showed that SCI provokes immediate changes in cortical spontaneous and evoked responses and here, we have performed a similar study to define the immediate changes produced in the thalamic ventro-postero-lateral nucleus (VPL) that are associated with the forepaw and hindpaw circuits. Extracellular electrophysiological recordings from the VPL reflected the spontaneous activity and the responses to peripheral electrical stimulation applied to the paws. Accordingly, the activity of the neuronal populations recorded at specific thalamic locations that correspond to the forepaw and hindpaw circuits was recorded under control conditions and immediately after thoracic SCI. The results demonstrate that peripheral inputs from both extremities overlap on neuronal populations in the somatosensory thalamus. In addition, they show that the responses of thalamic neurons to forepaw and hindpaw stimuli are increased immediately after SCI, in association with a specific decrease in spontaneous activity in the hindpaw locations. Finally, the increased thalamic responses after SCI have a state-dependent component in relation with cortical activity. Together, our results indicate that the thalamic changes occurring immediately after SCI could contribute to the cortical changes also detected immediately after such spinal lesions.

Increased cortical responses to forepaw stimuli immediately after peripheral deafferentation of hindpaw inputs.

Both central and peripheral injuries of the nervous system induce dramatic reorganization of the primary somatosensory cortex. We recently showed that spinal cord injuries at thoracic level in anesthetized rats can immediately increase the responses evoked in the forepaw cortex by forepaw stimuli (above the level of the lesion), suggesting that the immediate cortical reorganization after deafferentation can extend across cortical representations of different paws. Here we show that a complete deafferentation of inputs from the hindpaw induced by injury or pharmacological block of the peripheral nerves in anesthetized rats also increases the responses evoked in the forepaw cortex by forepaw stimuli. This increase of cortical responses after peripheral deafferentation is not associated with gross alterations in the state of cortical spontaneous activity. The results of the present study, together with our previous works on spinal cord injury, suggest that the forepaw somatosensory cortex is critically involved in the reorganization that starts immediately after central or peripheral deafferentation of hindpaw inputs.

Functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection in rats.

Spinal cord injury may produce long-term reorganization of cortical circuits. Little is known, however, about the early neurophysiological changes occurring immediately after injury. On the one hand, complete thoracic spinal cord transection of the spinal cord immediately decreases the level of cortical spontaneous activity and increases the cortical responses to stimuli delivered to the forepaw, above the level of the lesion. On the other hand, a thoracic spinal cord hemisection produces an immediate cortical hyperexcitability in response to preserved spinothalamic inputs from stimuli delivered to the hindpaw, below the level of the lesion. Here we show that a thoracic spinal cord hemisection also produces a bilateral increase of the responses evoked in the forepaw cortex by forepaw stimuli, associated with a bilateral decrease of cortical spontaneous activity. Importantly, the increased cortical forepaw responses are immediate in the cortex contralateral to the hemisection (significant within 30min after injury), but they are progressive in the cortex ipsilateral to the hemisection (reaching significance only 2.5h after injury). Conversely, the decreased cortical spontaneous activity is progressive both ipsilaterally and contralaterally to the hemisection (again reaching significance only 2.5h after injury). In synthesis, the present work reports a functional reorganization of the forepaw cortical representation immediately after thoracic spinal cord hemisection, which is likely important to fully understand the mechanisms underlying long-term cortical reorganization after incomplete spinal cord injuries.

Spinal cord injury immediately decreases anesthetic requirements in rats.

STUDY DESIGN: Pharmacologically blocking the spinal cord produces sedative effects and reduces anesthesia requirements in patients and animals. Whether spinal cord injury also reduces anesthesia requirements remains unclear. METHODS: We retrospectively analyzed data from urethane-anesthetized rats (15) to assess anesthesia requirements immediately after complete thoracic transection of the spinal cord. The depth of anesthesia was monitored up to 12 h after spinal transection by the reflexes to noxious stimuli and by electrophysiological recordings from the infragranular layers of the primary somatosensory cortex. Whenever animals displayed electrophysiological and/or behavioral signs of activation, we delivered an additional dose of anesthesia. Anesthetic requirements in animals receiving spinal transection (n=11) were compared with control animals receiving 'sham' lesion (n=9). RESULTS: The cumulative dose necessary to maintain a stable level of anesthesia was significantly lower in transected animals compared with control animals. By about 7 h after spinal cord injury, on average the cumulative dose of urethane was only 1.13±0.14 of the original dose, compared with 1.64±0.19 of the original dose in control animals. CONCLUSIONS: Spinal transection immediately decreased anesthetic requirements in rats. To establish whether these results are relevant for patients with spinal cord injury will require further investigation.